{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T21:41:11Z","timestamp":1760823671445,"version":"build-2065373602"},"reference-count":10,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"unspecified","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer AG","doi-asserted-by":"crossref","award":["Not Applicable"],"award-info":[{"award-number":["Not Applicable"]}],"id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,3,4]]},"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To describe opportunities and challenges experienced from the four pharmacoepidemiological database studies included in the rivaroxaban post authorisation safety study (PASS) programme and propose ways to maximise the value of population-based observational research when addressing regulatory requirements.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>PASS programme of rivaroxaban carried out as part of the regulatory postapproval commitment to the European Medicines Agency.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Clinical practice in Germany, the Netherlands, Sweden and the UK (electronic health records)\u2014undertaken by pharmacoepidemiology research teams using country-specific databases with different coding structures.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>355\u2009152 patients prescribed rivaroxaban and 338\u2009199 patients prescribed vitamin K antagonists.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Two major challenges that were encountered throughout the lengthy PASS programme were related to: (1) finalising country-tailored study designs before the extent of rivaroxaban uptake was known, and (2) new research questions that arose during the programme (eg, those relating to an evolving prescribing landscape).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Recommendations<\/jats:title>\n                  <jats:p>We advocate the following strategies to help address these major challenges (should they arise in any future PASS): conducting studies based on a common data model that enable the same analytical tools to be applied when using different databases; maintaining early, clear, continuous communication with the regulator (including discussing the potential benefit of studying drug use as a precursor to planning a safety study); consideration of adaptive designs whenever uncertainty exists and following an initial period of data collection; and setting milestones for the review of study objectives.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-081348","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T00:16:27Z","timestamp":1711412187000},"page":"e081348","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Challenges and lessons learned from a long-term postauthorisation safety study programme of rivaroxaban in Europe"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7446-9851","authenticated-orcid":false,"given":"Gunnar","family":"Brobert","sequence":"first","affiliation":[{"name":"Bayer AG, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Ruigomez","sequence":"additional","affiliation":[{"name":"Spanish Centre for Pharmacoepidemiologic Research, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0224-1866","authenticated-orcid":false,"given":"Tania","family":"Schink","sequence":"additional","affiliation":[{"name":"Leibniz-Institut f\u00fcr Pr\u00e4ventionsforschung und Epidemiologie\u2014BIPS GmbH, Bremen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8109-1108","authenticated-orcid":false,"given":"Annemarie","family":"Voss","sequence":"additional","affiliation":[{"name":"Leibniz-Institut f\u00fcr Pr\u00e4ventionsforschung und Epidemiologie\u2014BIPS GmbH, Bremen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2561-8734","authenticated-orcid":false,"given":"Ron","family":"Herings","sequence":"additional","affiliation":[{"name":"PHARMO Institute for Drug Outcomes Research, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1882-4748","authenticated-orcid":false,"given":"Elisabeth","family":"Smits","sequence":"additional","affiliation":[{"name":"PHARMO Institute for Drug Outcomes Research, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin M A","family":"Swart","sequence":"additional","affiliation":[{"name":"PHARMO Institute for Drug Outcomes Research, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7453-0157","authenticated-orcid":false,"given":"Leif","family":"Friberg","sequence":"additional","affiliation":[{"name":"Friberg Research AB, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5065-4788","authenticated-orcid":false,"given":"Yanina","family":"Balabanova","sequence":"additional","affiliation":[{"name":"Bayer AG, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Tarenz","sequence":"additional","affiliation":[{"name":"Bayer AG, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3189-6378","authenticated-orcid":false,"given":"Kiliana","family":"Suzart-Woischnik","sequence":"additional","affiliation":[{"name":"Bayer AG, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3825-0182","authenticated-orcid":false,"given":"Montse","family":"Soriano-Gabarr\u00f3","sequence":"additional","affiliation":[{"name":"Bayer AG, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5822-2453","authenticated-orcid":false,"given":"Pareen","family":"Vora","sequence":"additional","affiliation":[{"name":"Bayer AG, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Homering","sequence":"additional","affiliation":[{"name":"Bayer AG, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Dyszynski","sequence":"additional","affiliation":[{"name":"Bayer AG, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerd","family":"Nagel","sequence":"additional","affiliation":[{"name":"Bayer AG, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Amaya","sequence":"additional","affiliation":[{"name":"Bayer AG, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0837-2709","authenticated-orcid":false,"given":"Luis Alberto","family":"Garc\u00eda Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Spanish Centre for Pharmacoepidemiologic Research, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"2025101814083032000_14.3.e081348.1","unstructured":"Xarelto summary of product characteristics. 2019. 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